In an attempt to regenerate an impaired and defective biological tissue, the research and development of a structure that functions as a scaffold for tissues and cells has been ongoing in recent years as a part of the regenerative medicine. As a structure that functions as a scaffold, sponge, honeycomb, fiber structures wherein fibers are multi-layered such as non-woven fabric and the like, films and coatings are known.
Medical materials such as scaffold for tissues and cells desirably have biodegradability and biocompatibility in combination. From such aspect, many production examples of medical materials using collagen, gelatin, cellulose, chitin, chitosan, polylactic acid and the like are disclosed. For example, as a fiber structure medical material, those using chitosan, chondroitin sulfate, polysaccharides such as pectin and the like are disclosed (patent document 1). A fiber structure can be generally formed by a method called electrospinning method. A polymer compound is dissolved in a solvent to give a solution, the polymer compound solution is discharged under application of a high voltage to form a fiber, and the fiber is accumulated on a substrate (collector), whereby a fiber structure can be obtained. A fiber structure produced using chitosan under controlled production conditions of such electrospinning method is also disclosed (patent documents 2, 3). However, all the above-mentioned fiber structures do not have a desirable shape as a fiber structure, even though they are medical materials provided with biodegradability. For example, the width of the fiber diameter may be extremely nonuniform, or bonding of fibers may be observed. Even if the width of the fiber diameter could be controlled, the production conditions are impractical since the fiber formation stage requires a markedly long time and the like. In some cases, moreover, since chitosan is not completely dissolved in the solution, a satisfactory fiber structure is unattainable.
As for fiber structures, a method using poly-γ-benzyl-L-glutamic acid as a material is disclosed (non-patent document 1). In this method, the fiber diameter is controlled by dissolving the material at a low concentration in an organic solvent with low polarity, thereby suppressing interactions between molecules. However, formation of the fiber becomes difficult when the concentration of the solution reaches some low levels, and the fiber diameter has not actually been reduced to a satisfactory thinness. When a fiber structure is used as a medical material, it is desirably constituted by a thinner fiber, particularly nanometer-order fiber (nanofiber), in view of the degradability in the live body. However, a fiber structure made of a thin fiber such as nanofiber requests precise control of the production conditions, materials to be used and the like, which makes production by an electrospinning method difficult to achieve.
As other biodegradable materials, a fiber structure medical material using polylactic acid is disclosed (patent document 4). However, in this fiber structure, a nanometer-order fiber diameter has not been actually achieved. It is also suggested that polylactic acid lacks flexibility, is poor in compatibility with soft tissues, and causes inflammatory reaction in the live body, and therefore, is not a biodegradable material sufficiently safe as a medical material.
Besides the fiber structure, films and coatings are utilized, and a single cell culture obtained by forming a film from extracellular matrix components such as collagen, fibronectin and laminin (patent document 5), and a cell culture vessel coated with a similar extracellular matrix component are disclosed (patent document 6). However, extracellular matrix components are highly unstable and the property may be degraded in about several months even by chilled storage. Among the extracellular matrix components, collagen is widely used. However, the problems of BSE (bovine spongiform encephalopathy), foot-and-mouth disease and the like have made the use thereof difficult, and collagen itself is easily denatured in a production step such as film formation and the like. In the current situation, therefore, handling of collagen while maintaining its inherent function is difficult. To confer strength, formaldehyde and glutaraldehyde may be used for crosslinking. However, since these organic substances show extremely high toxicity, they are problematic in safety.
Patent document 7 describes a cell culture film made from a copolymer of polyamino acid and urethane. Non-patent documents 2 and 3 describe that a resin made from a random copolymer of 3 kinds of amino acids (glutamic acid, lysine, leucine) grow hepatocytes with good cell adhesiveness. Furthermore, non-patent document 4 describes that a laminate film of α-polyglutamic acid and chitosan shows good adhesiveness to one of myoblasts, and promotes growth. In recent years, however, a practical material that promotes differentiation of undifferentiated cell is increasingly desired along with the development of the study of iPS cells, and a material satisfying such demand has not been found.